rs4587626

Variant names:

• chr10-66470589-C-A
• rs4587626
• NM_013266.4:c.1531+50028G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1531+50028G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 151,774 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.062 (608 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 2 publications found

Genes affected

CTNNA3 (HGNC:2511): (catenin alpha 3) This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

CTNNA3 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1531+50028G>T		intron_variant	Intron 11 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1531+50028G>T		intron_variant	Intron 11 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9359 AN: 151660 Hom.: 607 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0618 AC: 9387 AN: 151774 Hom.: 608 Cov.: 32 AF XY: 0.0601 AC XY: 4457 AN XY: 74170

African (AFR) AF: 0.165 AC: 6825 AN: 41382

American (AMR) AF: 0.0225 AC: 342 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3466

East Asian (EAS) AF: 0.0648 AC: 334 AN: 5154

South Asian (SAS) AF: 0.0555 AC: 267 AN: 4812

European-Finnish (FIN) AF: 0.0263 AC: 278 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0170 AC: 1157 AN: 67876

Other (OTH) AF: 0.0414 AC: 87 AN: 2102

Alfa AF: 0.0290 Hom.: 236

Bravo AF: 0.0657

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.88
DANN	Benign	0.19
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4587626; hg19: chr10-68230347;